To investigate the role of endogenous vertebrate lectins in the maturation, metabolism and transport of cellular glycoproteins, we have synthesized phenyl-azido-lactose (PAL), a photolabile derivative of a specific hapten carbohydrate which can act as a photoaffinity inhibitor of lectin activity. This derivative and lactose have similar affinities with respect to endogenous lectin inactivation. It is internalized by endocytosis, but is not metabolized by the cell. We have also developed a sensitive assay to distinguish between active or PAL-inactivated forms of the lactose-specific lectin, based on the reaction of lectin cysteinyl residues with tritiated N-ethyl maleimide and affinity chromatography. To study the molecular basis for the increased protease sensitivity of nonglycosylated proteins, we investigated the possibility that aspariginyl residues can participate in the recruitment of proteins for degradation. Reticulocycte lysates catalyze the covalent binding of ubiquitin to polyasparagine, and the ATP-dependent binding of ubiquitin stimulates the proteolysis of this homopolymer by 3-5 fold.